Q99988 (GDF15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Growth/differentiation factor 15
Short name=GDF-15

Alternative name(s):
Macrophage inhibitory cytokine 1
Short name=MIC-1
NSAID-activated gene 1 protein
Short name=NAG-1
NSAID-regulated gene 1 protein
Short name=NRG-1
Placental TGF-beta
Placental bone morphogenetic protein
Prostate differentiation factor

Gene names

Name:	GDF15
Synonyms:	MIC1, PDF, PLAB, PTGFB

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	308 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Subunit structure	Homodimer; disulfide-linked By similarity.
Subcellular location	Secreted Probable.
Tissue specificity	Highly expressed in placenta, with lower levels in prostate and colon and some expression in kidney.
Sequence similarities	Belongs to the TGF-beta family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell signaling Traceable author statement Ref.3. Source: ProtInc transforming growth factor beta receptor signaling pathway Traceable author statement Ref.2. Source: ProtInc
Cellular_component	extracellular region Traceable author statement Ref.3. Source: ProtInc extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	cytokine activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 29	29	Potential
	Propeptide	30 – 194	165	Potential		PRO_0000033992
	Chain	195 – 308	114	Growth/differentiation factor 15		PRO_0000033993
Amino acid modifications
	Glycosylation	70	1	N-linked (GlcNAc...) Potential
	Disulfide bond	211 ↔ 274		By similarity
	Disulfide bond	240 ↔ 305		By similarity
	Disulfide bond	244 ↔ 307		By similarity
	Disulfide bond	273		Interchain By similarity
Natural variations
	Natural variant	9	1	V → L. Ref.2 Ref.3 Ref.4 Ref.5 Corresponds to variant rs1059519 [ dbSNP | Ensembl ].		VAR_047646
	Natural variant	48	1	S → T. Ref.2 Ref.3 Ref.5 Corresponds to variant rs1059369 [ dbSNP | Ensembl ].		VAR_010386
	Natural variant	202	1	H → D. Ref.1 Corresponds to variant rs1058587 [ dbSNP | Ensembl ].		VAR_047647
Experimental info
	Sequence conflict	269	1	V → E in AAB88913. Ref.1
	Sequence conflict	288	1	T → A in AAF89834. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Q99988 [UniParc]. Last modified November 30, 2010. Version 3. Checksum: 2FF3959021B95238	FASTA	308	34,140
	10 20 30 40 50 60 MPGQELRTVN GSQMLLVLLV LSWLPHGGAL SLAEASRASF PGPSELHSED SRFRELRKRY 70 80 90 100 110 120 EDLLTRLRAN QSWEDSNTDL VPAPAVRILT PEVRLGSGGH LHLRISRAAL PEGLPEASRL 130 140 150 160 170 180 HRALFRLSPT ASRSWDVTRP LRRQLSLARP QAPALHLRLS PPPSQSDQLL AESSSARPQL 190 200 210 220 230 240 ELHLRPQAAR GRRRARARNG DHCPLGPGRC CRLHTVRASL EDLGWADWVL SPREVQVTMC 250 260 270 280 290 300 IGACPSQFRA ANMHAQIKTS LHRLKPDTVP APCCVPASYN PMVLIQKTDT GVSLQTYDDL LAKDCHCI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PLAB, a novel placental bone morphogenetic protein." Hromas R., Hufford M., Sutton J., Xu D., Li Y., Lu L. Biochim. Biophys. Acta 1354:40-44(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASP-202. Tissue: Placenta.
[2]	"Human cDNA encoding a novel TGF-beta superfamily protein highly expressed in placenta." Yokoyama-Kobayashi M., Saeki M., Sekine S., Kato S. J. Biochem. 122:622-626(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-9 AND THR-48. Tissue: Fibrosarcoma.
[3]	"MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily." Bootcov M.R., Bauskin A.R., Valenzuela S.M., Moore A.G., Bansal M., He X.Y., Zhang H.P., Donnellan M., Mahler S., Pryor K., Walsh B.J., Nicholson R.C., Fairlie W.D., Por S.B., Robbins J.M., Breit S.N. Proc. Natl. Acad. Sci. U.S.A. 94:11514-11519(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-9 AND THR-48.
[4]	"Cloning and characterization of a novel member of the transforming growth factor-beta/bone morphogenetic protein family." Paralkar V.M., Vail A.L., Grasser W.A., Brown T.A., Xu H., Vukicevic S., Ke H.Z., Qi H., Owen T.A., Thompson D.D. J. Biol. Chem. 273:13760-13767(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LEU-9. Tissue: Placenta.
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS LEU-9 AND THR-48.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[7]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle.
[10]	"Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta." Lawton L.N., de Fatima Bonaldo M., Jelenc P.C., Qiu L., Baumes S.A., Marcelino R.A., de Jesus G.M., Wellington S., Knowles J.A., Warburton D., Brown S., Soares M.B. Gene 203:17-26(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 14-308.
[11]	"Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities." Baek S.J., Kim K.S., Nixon J.B., Wilson L.C., Eling T.E. Mol. Pharmacol. 59:901-908(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 264-308.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	U88323 mRNA. Translation: AAB88913.1. AB000584 mRNA. Translation: BAA19151.1. AF019770 mRNA. Translation: AAB88673.1. AF003934 mRNA. Translation: AAC24456.1. AK291530 mRNA. Translation: BAF84219.1. BT019465 mRNA. Translation: AAV38272.1. AC008397 Genomic DNA. No translation available. CH471106 Genomic DNA. Translation: EAW84694.1. BC000529 mRNA. Translation: AAH00529.1. BC008962 mRNA. Translation: AAH08962.1. AF008303 Genomic DNA. Translation: AAC39537.1. AF173860 mRNA. Translation: AAF89834.1.
IPI	IPI00306543.
PIR	JC5697.
RefSeq	NP_004855.2. NM_004864.2.
UniGene	Hs.616962.
3D structure databases
ProteinModelPortal	Q99988.
SMR	Q99988. Positions 209-307.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99988. 2 interactions.
STRING	9606.ENSP00000252809.
PTM databases
PhosphoSite	Q99988.
Polymorphism databases
DMDM	215273988.
Proteomic databases
PaxDb	Q99988.
PeptideAtlas	Q99988.
PRIDE	Q99988.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000252809; ENSP00000252809; ENSG00000130513. ENST00000595973; ENSP00000470531; ENSG00000130513.
GeneID	9518.
KEGG	hsa:9518.
UCSC	uc002niv.2. human.
Organism-specific databases
CTD	9518.
GeneCards	GC19P018496.
H-InvDB	HIX0014912.
HGNC	HGNC:30142. GDF15.
HPA	HPA011191.
MIM	605312. gene.
neXtProt	NX_Q99988.
PharmGKB	PA134866647.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG235805.
HOGENOM	HOG000143379.
HOVERGEN	HBG051718.
InParanoid	Q99988.
KO	K05504.
OMA	SWDVTRP.
OrthoDB	EOG46HGBQ.
PhylomeDB	Q99988.
Gene expression databases
Bgee	Q99988.
CleanEx	HS_GDF15.
Genevestigator	Q99988.
GermOnline	ENSG00000130513. Homo sapiens.
Family and domain databases
InterPro	IPR001839. TGF-b_C. IPR015615. TGF-beta-rel. [Graphical view]
PANTHER	PTHR11848. PTHR11848. 1 hit.
Pfam	PF00019. TGF_beta. 1 hit. [Graphical view]
SMART	SM00204. TGFB. 1 hit. [Graphical view]
PROSITE	PS00250. TGF_BETA_1. False negative. PS51362. TGF_BETA_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	GDF15. human.
GenomeRNAi	9518.
NextBio	35670.
PMAP-CutDB	Q9BWA0.
SOURCE	Search...

Entry information

Entry name

GDF15_HUMAN

Accession

Primary (citable) accession number: Q99988
Secondary accession number(s): O14629 , P78360, Q9BWA0, Q9NRT0

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 115 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.